Pancratistatin 1, a member of the Amaryllidaceae group of alkaloids, originates from plants used in herbal folk medicine as long ago as ancient Grecian times).sup.1,2 Structures of pancratistatin and its congeners have been elucidated by Pettit;.sup.3 some have been synthesized,.sup.4 although to date only one synthesis of racemic pancratistatin, by Danishefsky, has been reported..sup.5 This synthesis is not satisfactory for commercial scale up because it involves at least 26 steps, is racemic, and involves a large number of functional group manipulations. Approaches to pancratistatin and lycoricidine (a congener of pancratistatin) are known in the literature..sup.6 Pancratistatin exhibits promising antimitotic activities associated with other Amaryllidaceae alkaloids as well..sup.1,7 The established spectrum of biological activity of pancratistatin includes inhibition of protein synthesis and antineoplastic activities in ovarian sarcoma and lymphatic leukemia..sup.2 Its natural abundance is low (0.039% of the dry weight of ground roots of Pancratium littorale),.sup.2 and the completion of biological screening would benefit from an efficient synthesis of this compound and closely related compounds.
Despite the desirability to synthesize pancratistatin and related compounds, efficient methods have heretofore been unavailable. Particularly, there has been no previous disclosure of an asymetric synthetic approach for (+)-pancratistatin. Therefore, it is an object of the present invention to provide a general method for the synthesis of pancratistatin and related compounds.
It is a further object of the present invention to provide an asymetric method for synthesis of pancratistatin, preferably by a method which can yield the product in a minimum number of steps.
These and other objects of the present invention will become apparent upon review of the following specification and claims appended thereto.